The long-term objective of this study is to provide a better understanding of the pathogenesis of vascular occlusion in sickle cell anemia, by establishing the physiologic importance of rheologic properties in governing the passage of sickle cells through the capillary and precapillary microcirculation. The specific aims are 1. to study the ability of individual sickle cells to deform and "tank-tread" in the rheoscope as a function of cell density and environmental pO2; 2. to deduce intrinsic membrane mechanical properties (shear modulus of elasticity, shear viscosity) from reheoscopic observation of motion and deformation (a) under steady state shear flow and (b) during shape recovery following abrupt cessation of flow; 3. to characterize the changes in the rheological behavior of (a) hemoglobin A and S solutions and (b) normal and sickle cell suspensions in the course of oxygenation-deoxygenation; relate the observed behavior to the kinetics of polymerization-depolymerization of sickle hemoglobin, delineating the influence on the cell membrane; determine the effect of shearing on the kinetics as well as on the equilibrated suspensions; and 4. to relate any variability in rheologic properties of sickle cells from different individuals to the patient's clinical status and specific hemoglobinopathy. Direct microscopic observations and video recording of red cells tank-treading at various stresses will be accomplished by means of a counter-rotating cone-plate rheoscope. Steady state elongation, tank-treading frequency and recovery time of individual cells are to be measured and the intrinsic membrane and cytoplasmic properties calculated by appropriate mathematical models. A Weissenberg Rheogoniometer, modified to allow step changes in pO2, will be used to measure rheologic properties of sickle hemoglobin solutions and cell suppensions under quiescent and shearing conditions. The reaction kinetics of hemoglobin polymerization will be also studied by an ultrasonic shearing technique.